Several mechanisms have been found which appear to be involved in the regulation of tetrahydrobiopterin (BH4) biosynthesis. In the adrenergic neuroblastoma cell line, NIE115, BH4 synthesis was found to be inhibited by pterins including BH4, folate and dihydrofolate. In rats, evidence was obtained which indicates that phenylalanine is capable of stimulating the synthesis of BH4.